The imbalance between cell division and cell death during organ development can lead to cell transformation and tumorigenesis. The breast, a glandular epithelium, undergoes constant remodeling due to hormonal changes during a woman's life. This process, including elongation, branching, lactation, and involution, is regulated by proliferation and cell death cycles. Any imbalance in these events can result in the transformation of epithelial cells. Several studies suggest that the molecular events during breast morphogenesis can provide clues for managing breast cancer. However, the molecular signalling and regulation of breast morphogenesis remain largely unexplored. Apoptosis Inhibitor 5 (Api5) is an anti-apoptotic protein that is upregulated in cancers, including breast cancer. Api5 regulates various signaling pathways involved in apoptosis, such as caspase-3 mediated acinus cleavage, caspase-2 activation, E2F1-mediated apoptotic signalling, and ERK-mediated Bim degradation. ERK signalling and Bim regulation are essential for breast morphogenesis, while E2F1 regulates cell cycle and apoptosis and functions as a transcription factor for several genes. This study proposes to identify the role of Api5 during breast morphogenesis using 3D breast acinar cultures as a model system. The mechanism of Api5's role will be studied using small-molecule chemical inhibitors. The results may provide novel biomarkers and drug targets for managing breast cancer.
Indian Institute of Science
Acces sibility Controls